The present invention relates to immunogenic compositions for inducing protective antibodies against Helicobacter spp. infection. It also relates to proteinaceous material derived from Helicobacter, and to nucleic acid sequences encoding them. Antibodies to these proteinaceous materials are also included in the invention.
H. pylori is a microorganism, which infects human gastric mucosa and is associated with active chronic gastritis. It has been shown to be an aetiological agent in gastroduodenal ulceration (Peterson, 1991), and two recent studies have reported that persons infected with H. pylori had a higher risk of developing gastric cancer (Nomura et al., 1991; Parsonnet et al., 1991).
In vivo studies of the bacterium, and consequently, work on the development of appropriate preventive or therapeutic agents, has been severely hindered by the fact that Helicobacter pylori only associates with gastric-type epithelium from very few animal hosts, none of which are suitable for use as laboratory models.
A mouse model of gastric colonization has been developed using a helical bacterium isolated from cat gastric mucus (Lee et al., 1988, 1990) and identified as a member of the genus Helicobacter. It has been named H. felis (Paster et al., 1990).
To date, only limited information concerning H. felis and the extent of its similarities and differences with H. pylori is available. The reliability of the mouse model for the development of treatments for H. pylori infection is, therefore, uncertain. Recently, it was shown that H. pylori urease is a protective antigen in the H. felis/mouse model (Davin et al., 1993; Corthesy-Theulaz et al., 1993).
It is, therefore, an aim of the present invention to provide therapeutic and preventive compositions for use in Helicobacter infection, which furthermore can be tested in laboratory animals.
It is known that H. pylori expresses urease activity and that urease plays an important role in bacterial colonization and mediation of certain pathogenic processes (Ferrero and Lee, 1991;
Hazel et al., 1991).
The genes coding for the urease structural polypeptides of H. pylori (UreA (SEQ ID NO:22), UreB (SEQ ID NO:26)) have been cloned and sequenced (Labigne et al., 1991; and French Patent Application FR 8813135), as have the genes coding the "accessory" polypeptides necessary for urease activity in H. pylori (International patent application WO 93/07273).
Attempts have been made to use nucleic acid sequences from the H. pylori urease gene cluster as probes to identify urease sequences in H. felis. However, none of these attempts have been successful. Furthermore, the establishment and maintenance of H. felis cultures in vitro is extremely difficult, and the large quantities of nucleases present in the bacteria complicates the extraction of DNA.